Age-dependent effects of the recombinant spike protein/SARS-CoV-2 on the M-CSF- and IL-34-differentiated macrophages in vitro.
Age-dependent effects of the recombinant spike protein/SARS-CoV-2 on the M-CSF- and IL-34-differentiated macrophages in vitro.
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重组峰值蛋白/SARS-COV-2对M-CSF和IL-34差异型巨噬细胞的年龄依赖性作用。
DOI：
10.1016/j.bbrc.2021.01.104
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发表时间：
2021-03-26
影响因子：
3.1
通讯作者：
Movila A
中科院分区：
文献类型：
--
作者：
Duarte C;Akkaoui J;Ho A;Garcia C;Yamada C;Movila A
SARS-CoV-2病毒引起巨噬细胞衰老相关分泌表型（SASP）标志物的产生升高。在组织蛋白酶（Cat） B和L的帮助下，SARS-CoV-2通过其spike蛋白进入巨噬细胞，这两种蛋白也介导SASP的产生。由于M-CSF和IL-34控制巨噬细胞分化，我们研究了spike蛋白对小鼠M-CSF和IL-34分化的巨噬细胞中sasp相关的促炎细胞因子和核衰老调节因子以及CatB、L和K的年龄依赖性影响。spike蛋白上调年轻和老年男性m - csf巨噬细胞中SASP的表达。相比之下，只有年轻和老年男性il -34巨噬细胞在体外对spike蛋白的反应中表现出明显的促炎细胞因子表达降低。此外，s蛋白升高了CatB在年轻男性m - csf巨噬细胞和年轻女性IL-34巨噬细胞中的表达，而CatL在年轻男性IL-34和老年男性m - csf巨噬细胞中过表达。令人惊讶的是，s蛋白增加了年轻和老年男性m - csf巨噬细胞中CatK的活性，表明CatK可能也参与了COVID-19的病理。总之，我们利用一种新型的SARS-CoV-2/COVID-19体外小鼠模型证明了spike蛋白对M-CSF和il -34巨噬细胞的年龄和性别依赖性作用。
The SARS-CoV-2 virus causes elevated production of senescence-associated secretory phenotype (SASP) markers by macrophages. SARS-CoV-2 enters macrophages through its Spike-protein aided by cathepsin (Cat) B and L, which also mediate SASP production. Since M-CSF and IL-34 control macrophage differentiation, we investigated the age-dependent effects of the Spike-protein on SASP-related pro-inflammatory-cytokines and nuclear-senescence-regulatory-factors, and CatB, L and K, in mouse M–CSF– and IL-34-differentiated macrophages. The Spike-protein upregulated SASP expression in young and aged male M–CSF–macrophages. In contrast, only young and aged male IL-34-macrophages demonstrated significantly reduced pro-inflammatory cytokine expression in response to the Spike-protein in vitro. Furthermore, the S-protein elevated CatB expression in young male M–CSF–macrophages and young female IL-34-macrophages, whereas CatL was overexpressed in young male IL-34- and old male M–CSF–macrophages. Surprisingly, the S-protein increased CatK activity in young and aged male M–CSF–macrophages, indicating that CatK may be also involved in the COVID-19 pathology. Altogether, we demonstrated the age- and sex-dependent effects of the Spike-protein on M-CSF and IL-34-macrophages using a novel in vitro mouse model of SARS-CoV-2/COVID-19.
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影响因子：
4.9
作者：
Garcia S;Hartkamp LM;Malvar-Fernandez B;van Es IE;Lin H;Wong J;Long L;Zanghi JA;Rankin AL;Masteller EL;Wong BR;Radstake TR;Tak PP;Reedquist KA
通讯作者：
Reedquist KA
SARS 冠状病毒刺突蛋白的蛋白水解激活：抗病毒研究前沿的切割酶。
影响因子：
7.6
作者：
Simmons, Graham;Zmora, Pawel;Gierer, Stefanie;Heurich, Adeline;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
4.3
作者：
Hao L;Chen J;Zhu Z;Reddy MS;Mountz JD;Chen W;Li YP
通讯作者：
Li YP
影响因子：
3.8
作者：
Segaliny, Aude I.;Brion, Regis;Heymann, Dominique
通讯作者：
Heymann, Dominique
影响因子：
5.6
作者：
Akkaoui, Juliet;Yamada, Chiaki;Movila, Alexandru
通讯作者：
Movila, Alexandru